HAPLOTYPES OF THE APOA-I C-III/A-IV GENE-CLUSTER AND FAMILIAL COMBINED HYPERLIPIDEMIA/

Familial combined hyperlipidemia (FCHL) is the most frequent familial lipoprotein disorder associated with premature coronary heart disease. However, no genetic defect(s) underlying FCHL has been identified, A linkage between FCHL and the apoA-I/C-III/A-IV gene cluster has been r eported but not verified in other populations. A recent study identifi ed FCHL susceptibility haplotypes at this gene cluster, To study wheth er such haplotypes are also associated with FCHL susceptibility in Fin ns, we studied 600 well-defined Finnish FCHL patients and their relati ves belonging to 28 extended FCHL families by using haplotype, linkage , sib-pair, and linkage disequilibrium analyses, The genotypes of the MspI polymorphisms were associated with total serum cholesterol (P<0.0 1) and apoB (P<0.05) levels in spouses, which represent the general Fi nnish population, However, no evidence of direct involvement of any of these loci or their specific haplotypes in the expression of FCHL in the Finnish FCHL families was found.